Arterial and venous blood pressures in hemodialysis and other extracorporeal tube sets have traditionally been measured indirectly via a blood/air interface and air column communicating with a pressure measuring transducer. Such interface is typically located in an air trap chamber. The air column typically is contained within and communicates between various components: the top of a chamber, a pressure monitor tube (PMT), a dialysis machine tubing and a pressure measuring transducer housing within the dialysis machine. Also known are blood/air interfaces without a chamber where a PMT communicates with a blood tube at a xe2x80x9cTxe2x80x9d connection.
Each air column typically comprises a sterile chamber/PMT portion and an unsterile machine portion. A sterility barrier (or transducer protector), capable of transmitting air pressure while maintaining sterility, separates the sterile chamber/PMT portion from each unsterile machine portion. Typically the sterility barrier is a hydrophobic membrane permeable to air flow but not to aqueous liquids. Typically, the air column has a large cross section in the air trap chamber (10-35 mm ID) and a narrow cross section in the PMT (0.5-3.5 mm ID).
Such blood/air interfaces have numerous problems. First, blood exposed to air activates a clotting cascade, usually in direct proportion to the blood/air interface surface area and to the degree of stagnation of the blood at the interface. Anticoagulants such as heparin are required to counteract such clotting tendency. Anticoagulants are costly and have numerous side effects for the patient.
Second, air in conventional air trap chambers can escape and enter the patient, even if no air enters the chamber in the incoming blood flow. That is, if and when the blood/air interface falls below the blood inlet (e.g., a downspout) the incoming blood flow causes cavitation at the interface and entrains air emboli in the downward blood flow, such that the air may escape the air trap chamber.
Third, air trap chambers often comprise over 20 percent of the size, weight and cost of the entire blood tubing set.
The fourth problem relates to blood/air interface level changes in the chamber due to pressure reductions (where liquid level goes down) and pressure increases (where liquid level goes up). Such level changes promote a risk of inhibiting accurate pressure measurements and may promote air emboli passing to the patient. The degree of blood/air interface level change is in direct proportion to the total volume of air in both the tube set and pressure machine portions according to Boyle""s law. Machine air volumes typically vary from 2 cc to more than 10 cc, depending on manufacturer and model. PMT air volumes typically range from 0.5 cc to 6 cc. Chamber air volumes depend on the blood level chosen by the clinician, but typically range from 3 cc to 20 cc. With the blood pump off, blood pressures are zero, and the arterial and venous blood/air interfaces are at the level in the chamber initially chosen by the clinician. But when blood flows increase to typical speeds (e.g. 450 ml/min with 15 G AVF needles), pre-pump pressures drop as much as xe2x88x92300 mmHg or more and post-pump pressures increase as much as +500 mmHg.
In the positive pressure case, the air volume may be compressed as much as 40 percent or more ((1160 mmHgxe2x88x92760 mmHg)/760 mmHg). If the chamber/PMT air volume is less than 40 percent of the total air volume, the blood/air interface level can rise into the PMT until it is stopped by the transducer protector. Blood is thus trapped in the transducer protector and typically clots, and the machine transducer is no longer able to accurately measure pressure. This is a highly dangerous situation. In the negative pressure case, the air volume may be expanded as much as 65 percent or more (760 mmHg/(760 mmHgxe2x88x92300 mmHg)). If the chamber blood volume is less than the expansion air volume, the blood/air interface may fall until it empties the chamber and passes air to the patient, causing air emboli, an even more dangerous situation.
A fifth problem relates to dialysis tube sets and dialyzers requiring priming with physiologic fluid to eliminate unwanted air prior to processing blood through the circuit. In typical prior art chambers, an initial saline prime creates a saline/air interface in an upper portion of the chamber at a position chosen by the physician. When blood flow starts, however, saline is completely displaced by blood due to the excellent mixing in these chambers. Typically, the blood inlet is close to the saline/air interface or points at the saline/air interface. Thus, the saline/air interface quickly becomes a blood/air interface.
Other prior art chambers have long blood inlet downspouts or other arrangements to enter the chamber well below the fluid level in the chamber and pointed away from the fluid level. For example, Fresenius AG has an air trap chamber designed to promote a blood/saline or plasma/air interface with the blood inlet directed transversely and located well below the interface of the chamber. In these chambers, the initial saline/air interface may be set well above the blood inlet to the chamber. Blood is slightly heavier than saline (the cellular elements more so than plasma), so when blood enters the chamber (especially at low or moderate flow common in Europe and Japan), blood tends not to invade the stagnant (saline) area above the inlet level. This is often sufficient to stratify into a blood/saline/air interface or even stratify into a blood/plasma/air interface since plasma is almost the density of saline and will rise above blood""s cellular elements if relatively undisturbed. As saline-to-air contact initiates no clotting-cascade, and plasma-to-air contact has few if any initiators for clotting, this design is thought to provide clotting protection over a normal blood/air interface.
In practice, however, this approach has had little practical value. Dialysis has many events that cause abrupt pressure changes: peristaltic pump action at high flows (a large pressure pulse where flow instantaneously slows, stops or even reverses with each roller stroke); pump stoppages due to alarms; patient movements, patient coughing, line kinking, inadvertent clamping, etc. These pressure changes cause the fluid level to rise or fall rapidly. In those chambers which have large cross sectional areas, xe2x80x9cplug flowxe2x80x9d does not occur. Instead, blood xe2x80x9cburpsxe2x80x9d up into the stagnant plasma or saline layers, and displaces some or all of the plasma and/or saline. Now blood is in a stagnant area of the chamber with a blood/air interface, and significant clotting is created. xe2x80x9cPlug flowxe2x80x9d is the movement of two fluids in a tube as separate but intact bodies, such that an interface separating the two fluids is maintained. Plug flow is easier with relatively small ID tubes than larger tubes.
Sixth, a greater destroyer of a stable blood/plasma or saline interface in air trap chambers is air bubbles entrained in the incoming blood flow. These bubbles rise to the surface, passing through any saline or plasma layers because the cross sectional area of these chambers is much larger than the diameter of these bubbles. If bubbles enter a tube small enough that the bubble bridges from wall to wall, frictional forces stop the bubble from rising further, unless convective forces push on the fluid column. The bubble locks the fluid above the bubble from mixing with the fluid below the bubble (as artfully employed by clinical analyzers). Bubbles of less diameter than the tube they are carried in, however, will freely rise. Due to the non-airfoil shape of these bubbles, they drag up blood in their wake into the plasma/saline layers. It takes relatively few bubbles to completely displace essentially all plasma or saline with blood creating a stagnant blood/air interface. As above, this blood is now subject to the stagnation clotting cascade mechanism.
The prior art also includes Cobe machines that mate with a sterile cassette tube set with a non-porous, diaphragmatic sterility barrier mounted directly in an air trap chamber side wall, which eliminates the need for a pressure monitor tube. This set does, however, comprise a blood/air interface in the air trap chamber. Brugger et al U.S. Pat. No. 5,693,008 shows an arrangement of machine and tube set which eliminates the blood/air interface. Zanger U.S. Pat. No. 5,392,653 discloses blood pressure measurement without an blood/air interface, using a diaphragm in direct connection with a force transducer.
Another prior art of a Japanese company seeks to overcome the blood/air problem by interposing a low weight fat between the blood and air phases. It discloses injecting a low weight fat into each chamber. Because this fat""s density is significantly below that of blood or plasma, it floats on top and prevent a blood/air interface, and if the layer is disrupted by bubbles or pressure pulses, the fat again rises to become the air interface. It also claims that fat does not initiate any clotting cascade mechanism. The expense and pharmaceutical regulatory approval required of this approach has apparently prevented its use.
Worldwide, all hemodialysis machines in use today are designed for blood/air interface tube sets. These machines provide over 120 million dialyses per year for over 800,000 end stage renal disease patients. Recent disclosures of airless blood tubing sets will require new machines and many years to bring their benefits to a substantial number of patients. It is an objective of this invention to create tube sets and methods for all presently existing machines, and new machines, that eliminate the blood/air interface. It is also a preferred objective of this invention to reduce the amount of anticoagulant required to perform dialysis. It is a preferred objective of this invention to reduce clotting in the tube sets, putting the saline column at least partially in a tube that has an inner diameter that substantially promotes xe2x80x9cplug flowxe2x80x9d and keeps the saline in between the blood phase and the air phase. It is a preferred objective of this invention that no modification of the existing machines is required to use these tube sets and methods. Also by this invention, the number of tube set components can be reduced in number, size and cost.
By this invention, the blood/air interface can be eliminated while sensing pressure in blood flow tubing. The method comprises: placing an aqueous, typically physiological, isotonic, substantially cell-free solution, (typically normal medical saline solution or the like) into branch connection tubing that connects in branching relation with the blood flow tubing at one end, and connecting with a pressure transducer unit at its other end. An air volume is maintained to occupy a portion of the branch connection tubing which is adjacent to the other end near the pressure transducer unit. One then flows positively or negatively pressurized blood through the blood flow tubing. Thus, the pressure of the blood is communicated through the aqueous solution and then the air volume in the branch connection tubing to the pressure transducer unit, with the blood being spaced from the air volume.
Typically, substantially all of the branch connection tubing containing the aqueous solution and air volume has an inner diameter of substantially no more than 5 mm. One purpose of this is to facilitate continued separation of blood and the solution described above, when pressurized blood enters the branch connection tubing through the one end. Preferably, the inner diameter of the tubing will be substantially no more than 3.5 mm.
While the above facilitates the continued separation of blood and solution, a certain amount of mixing may take place in the branch connection tubing so that the aqueous, cell-free solution can become pink in the area adjacent to the blood-solution interface. For this and other reasons, it is preferred for a priming solution tube, which is connected to a source of priming solution, to be connected in branching relation with the branch connection tube. Thus, added portions of priming solution can be periodically added to push downwardly the aqueous solution in the branch connection tubing, which has become mixed with a small amount of blood, into the blood flow tubing during operation, so that the aqueous solution in the branch connection tubing can remain substantially blood cell-free.
In this invention, the blood/air interface of the prior art is thus replaced on a continuing basis by a blood/saline/air interface. A saline column (or other appropriate solution) is interposed during the priming procedure between the blood phase and the air phase. The saline column, saline/air interface and air column are located within the branch connection tubing communicating with a main blood flow tube, optionally with an enlarged chamber of the main blood flow tube. Preferably, such a blood chamber is filled completely (eliminating any blood/air interface), and is well mixed. Preferably, the branch connection tubing is sized to promote plug flow (so as to prevent the blood/saline interface from rapidly degrading with pressure pulses, alarms, patient movements and changes in blood pressure from atmospheric to operating pressures) and to resist free flow of air bubbles. Its inlet to the blood flow tubing may be positioned below the highest point in the chamber so as to resist entry of air bubbles.
The ratio of the saline volume in the chamber/PMT to the air volume in the system is sufficient to prevent transducer protectors of the pressure transducer unit from being wetted out in a positive pressure situation, or air being dumped into the main blood tube in a negative pressure situation. An in-line chamber may be added to the branch connection tubing to help accomplish this.
This invention may use a variety of designs and methods, with and without air trap chambers in the blood tubing or in branch saline or air tubing.
The aqueous solution may be formulated to be compatible with blood to suppress clotting, for example, by the addition of heparin or the like. The heparin line which is conventionally found in extracorporeal blood sets may be connected in another branching connection to the branch connection tubing, typically at a connection downstream of a branch connection with the source of added aqueous solution, for priming and patient fluid maintenance.
The branch connection tubing may, if desired, define an in-line chamber that preferably extends for no more than 10 percent (and typically less than 7 percent) of the length of the branch connection tubing. The purpose of this is to provide an increased volume to the branch connection tubing, to reduce the movement of particularly the interface between blood and the aqueous solution as blood pressure changes.
Also, it may be desirable for the branch connection tubing to comprise a flow-resisting constriction to slow movement of the interface boundary between the blood and aqueous solution upon pressure changes. Particularly, the flow-resisting constriction is preferably positioned at a portion of the branch connection tubing that carries the aqueous solution, farther up the tubing than blood would be expected to travel. Thus, the movement of the interface boundary between the blood and the aqueous solution may be slowed in a manner to reduce mixing of blood and solution at their interface in the event of large, sudden pressure changes. Preferably, the flow-resisting constriction is positioned at a portion of the branch connection tubing that carries the aqueous solution, to spare the blood from the stresses that might be encountered by passing through such restriction.
In another embodiment, the main blood flow tubing may comprise an enlarged chamber portion. The branch connection tube connects in branching relation with the blood flow tubing through a wall of the enlarged chamber portion. The enlarged chamber portion is preferably completely filled with aqueous solution at the end of priming of the set for use, and then it becomes completely filled with blood, except for air bubbles that may be trapped in the chamber during the use, and are periodically drawn away by a syringe through an injection site or branch tube, or through a hydrophobic vent, in conventional manner.
In this embodiment, the branch connection tube may have a proximal end portion which extends for a substantial distance into the enlarged chamber portion inwardly through its wall. In use, the interface boundary between the blood and aqueous fluid may occupy the proximal end portion.
The branch connection tube may be integral and nonseparable along its length from its connection to the main blood flow tubing, to the connector at its other end through which it connects with the pressure transducer unit. Alternatively, the branch connection tube may be separable into two or more serial components by means of a pair or pairs of engaging connectors in various ways as may be desired. For example, the branch connection tube may be separable by a pair of adjoining connectors positioned between a T- or Y-junction where a line to a source of priming solution connects with the branching tubing, and to the main blood tube, so that most of the branch connection tubing and its connected priming solution tube can be a separate set. Alternatively, the tube that connects between the priming solution and the branch connection tubing may be a separate set, while the branch connection tubing is integral with the main blood tube. As another alternative, the branch connection tubing may carry an in-line chamber comprising preferably less than ten percent of the length of the branch connection tubing, and the line connected to the source of aqueous, cell-free solution (priming solution) can connect to that chamber in a form of a branch connection.
Branch connection tubings may connect to the blood tube both upstream (negative pressure) and downstream (positive pressure) of roller pump tubing, or other tubing which engages another type of pump for pumping through the tubing. Each of these branch connection tubings may communicate with a pressure transducer so that upstream and/or downstream pressure from the pump can be measured. The tubings will each have an air filled section adjacent the transducer protector and an aqueous solution-filled section adjacent the blood tube in accordance with this invention. Also, if desired, tubing may connect to each of these tubings in branching connection to provide access to a source of aqueous, isotonic, substantially cell-free solution (such as normal saline solution) so that such solution may be applied to the branch connection tubing. This solution may also be added back to the blood after treatment by hemofiltration for example, to give the patient a desired hematocrit in the blood before returning the blood to the patient.
The invention of this application may be utilized in the particular sets and the process of automatic priming thereof that fall under the scope of the invention as described in Utterberg U.S. patent application Ser. No. 08/954,804, filed Oct. 21, 1997, entitled xe2x80x9cAutomatic Priming of Blood Setsxe2x80x9d. Now U.S. Pat. No. 5,951,870.